氯沙坦降低小鼠呼吸机相关性肺损伤及抑制肺组织内小窝蛋白-1及NOX_4的表达  

Losartan regulates oxidative stress via caveolin- 1 and NOX_4 in mice with ventilator-induced lung injury

作　　者：凌旭光[1] 娄安妮[1] 李洋[1] 杨仁强[1] 宁佐伟[2] 李旭[3] 

机构地区：[1]南方医科大学南方医院急诊科,广东广州510515 [2]南方医科大学南方医院消化内科,广东广州510515 [3]南方医科大学南方医院感染内科,广东广州510515

出　　处：《南方医科大学学报》2015年第12期1739-1744,共6页Journal of Southern Medical University

基　　金：广东省医学科学技术研究基金(WSTJJ20131215440102198206013242)

摘　　要：目的利用呼吸机过度通气建立小鼠机械性肺损伤模型,以血管紧张素II受体抑制剂氯沙坦进行干预,探讨氯沙坦对机械通气性肺损伤小鼠肺内小窝蛋白-1及氧化应激相关蛋白的调节。方法 36只雄性C57小鼠随机分为对照组、机械通气组、单纯药物对照组和治疗组,建模完成后分别检测各组小鼠急性肺损伤情况以及相关蛋白的表达和相互作用。结果机械通气组小鼠肺损伤Smith评分3.3,明显高于对照组(0.4)和单纯药物对照组(0.3),治疗组Smith评分2.3,较机械通气组明显降低(P<0.05);机械通气组小鼠肺组织内小窝蛋白-1和NOX4蛋白表达明显高于对照组及单纯药物对照组(P<0.05),荧光共染可见小窝蛋白-1及NOX4发生荧光重合,治疗组小鼠肺组织内上述蛋白表达较机械通气组明显降低(P<0.05),荧光共染提示小窝蛋白-1及NOX4荧光重合区域较机械通气组减少。结论在机械通气诱导的小鼠急性肺损伤模型中,氯沙坦可缓解机械通气诱导的肺损伤并抑制小窝蛋白-1及NOX4的表达及相互趋近作用。Objective To investigate the effect of losartan in regulating oxidative stress and the underlying mechanism in mice with ventilator- induced lung injury. Methods Thirty- six male C57 mice were randomly divided into control group, losartan treatment group, mechanical ventilation model group, and ventilation plus losartan treatment group. After the corresponding treatments, the lung injuries in each group were examined and the expressions of caveolin-1 and NOX4 in the lung tissues were detected. Results The mean Smith score of lung injury was significantly higher in mechanical ventilation model group（3.3）than in the control group（0.4）, and losartan treatment group（0.3）; the mean score was significantly lowered in ventilation plus losartan treatment group（2.3） compared with that in the model group（P〈0.05）. The expressions of caveolin-1 and NOX4 were significantly higher in the model group than in the control and losartan treatment groups（P〈0.05） but was obviously lowered after losartan treatment（P〈0.05）. Co- expression of caveolin- 1 and NOX4 in the lungs was observed in the model group, and was significantly decreased after losartan treatment. Conclusions Losartan can alleviate ventilator- induced lung injury in mice and inhibit the expression of caveolin-1 and NOX4 and their interaction in the lungs.

关 键 词：氯沙坦 小窝蛋白-1 机械通气 氧化应激 急性肺损伤 

分 类 号：R563[医药卫生—呼吸系统]